The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.
The traditional treatment for refractory status epilepticus includes diazepam, midazolam, valproic acid, thiopental and propofol. These medications fail to control seizure activity in 20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity. Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce the epileptiform burst discharges and after potential. Therefore, targeting the N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the treatment of refractory status epilepticus. The specific aim is to determine whether continuous infusion of ketamine as a first line agent for refractory status epilepticus is effective in controlling seizures. The central hypothesis of our proposal is that early treatment with ketamine will be much more efficacious in controlling refractory status compared to the traditional treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Patients will receive traditional drug infusions
Patients will receive loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached
UAB Department of Anesthesiology and Perioperative Medicine
Birmingham, Alabama, United States
Time taken for burst suppression
Average time for burst suppression
Time frame: Baseline to 1 hr
Time taken for termination of seizures
Average time for seizures to terminate
Time frame: Baseline to 24 hrs
Use of vasopressors
The need of vasopressors
Time frame: baseline to 72 hrs
Number of days on ventilator
Total number of days patient is on the ventilator
Time frame: Baseline to 72 hrs
Length of stay in ICU
Total number of days in the ICU
Time frame: Baseline to 72 hrs postoperatively
Use of parenteral or enteral nutrition
Nutrition provided through a feeding tube or catheter
Time frame: Baseline to 72 hrs postoperatively
Medical imaging results
MRI scans 7 to 10 days after burst suppression
Time frame: Post-op Day 2 to Post-op day 10
Mortality
death
Time frame: baseline to post-op day 10
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